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000140199 0247_ $$2doi$$a10.1093/cvr/cvy113
000140199 0247_ $$2pmid$$apmid:29726891
000140199 0247_ $$2pmc$$apmc:PMC6455920
000140199 0247_ $$2ISSN$$a0008-6363
000140199 0247_ $$2ISSN$$a1755-3245
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000140199 037__ $$aDZNE-2020-06521
000140199 041__ $$aEnglish
000140199 082__ $$a610
000140199 1001_ $$aBrown, Rosalind$$b0
000140199 245__ $$aUnderstanding the role of the perivascular space in cerebral small vessel disease.
000140199 260__ $$aOxford$$bOxford University Press$$c2018
000140199 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2018-05-02
000140199 264_1 $$2Crossref$$3print$$bOxford University Press (OUP)$$c2018-09-01
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000140199 520__ $$aSmall vessel diseases (SVDs) are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD. In healthy tissue, these spaces are proposed to form part of a complex brain fluid drainage system which supports interstitial fluid exchange and may also facilitate clearance of waste products from the brain. The pathophysiological signature of PVS and what this infers about their function and interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development in the brain has not been established. Here we discuss the potential of enlarged PVS to be a unique biomarker for SVD and related brain disorders with a vascular component. We propose that widening of PVS suggests presence of peri-vascular cell debris and other waste products that form part of a vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid space, leading to accumulation of toxins, hypoxia, and tissue damage. Here, we outline current knowledge, questions and hypotheses regarding understanding the brain fluid dynamics underpinning dementia and stroke through the common denominator of SVD.
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000140199 650_2 $$2MeSH$$aAnimals
000140199 650_2 $$2MeSH$$aBlood-Brain Barrier: physiopathology
000140199 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: diagnostic imaging
000140199 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: pathology
000140199 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: physiopathology
000140199 650_2 $$2MeSH$$aGlymphatic System: diagnostic imaging
000140199 650_2 $$2MeSH$$aGlymphatic System: pathology
000140199 650_2 $$2MeSH$$aGlymphatic System: physiopathology
000140199 650_2 $$2MeSH$$aHumans
000140199 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000140199 650_2 $$2MeSH$$aMicrovessels: diagnostic imaging
000140199 650_2 $$2MeSH$$aMicrovessels: pathology
000140199 650_2 $$2MeSH$$aMicrovessels: physiopathology
000140199 650_2 $$2MeSH$$aPrognosis
000140199 7001_ $$aBenveniste, Helene$$b1
000140199 7001_ $$aBlack, Sandra E$$b2
000140199 7001_ $$aCharpak, Serge$$b3
000140199 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b4$$udzne
000140199 7001_ $$aJoutel, Anne$$b5
000140199 7001_ $$aNedergaard, Maiken$$b6
000140199 7001_ $$aSmith, Kenneth J$$b7
000140199 7001_ $$aZlokovic, Berislav V$$b8
000140199 7001_ $$0P:(DE-HGF)0$$aWardlaw, Joanna M$$b9$$eCorresponding author
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000140199 773__ $$0PERI:(DE-600)1499917-1$$a10.1093/cvr/cvy113$$gVol. 114, no. 11, p. 1462 - 1473$$n11$$p1462-1473$$q114:11<1462 - 1473$$tCardiovascular research$$v114$$x0008-6363$$y2018
000140199 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455920
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000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.110.592725$$o10.1161/STROKEAHA.110.592725
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1046/j.0953-816x.2001.01793.x$$o10.1046/j.0953-816x.2001.01793.x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1189/jlb.0303114$$o10.1189/jlb.0303114
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20160604$$o10.1042/CS20160604
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.111.643080$$o10.1161/STROKEAHA.111.643080
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s40478-014-0169-8$$o10.1186/s40478-014-0169-8
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/CIRCRESAHA.117.311054$$o10.1161/CIRCRESAHA.117.311054
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/micc.12064$$o10.1111/micc.12064
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1172/JCI86950$$o10.1172/JCI86950
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20170981$$o10.1042/CS20170981
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1471-4159.2010.06958.x$$o10.1111/j.1471-4159.2010.06958.x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s12916-017-0793-9$$o10.1186/s12916-017-0793-9
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/BF00685305$$o10.1007/BF00685305
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cmet.2008.03.010$$o10.1016/j.cmet.2008.03.010
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.RES.43.6.854$$o10.1161/01.RES.43.6.854
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1172/JCI39733$$o10.1172/JCI39733
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.STR.0000163080.82766.eb$$o10.1161/01.STR.0000163080.82766.eb
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3174/ajnr.A4888$$o10.3174/ajnr.A4888
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/jmri.22209$$o10.1002/jmri.22209
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/jnen/62.2.154$$o10.1093/jnen/62.2.154
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jns.2008.12.036$$o10.1016/j.jns.2008.12.036
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1155/2017/9372050$$o10.1155/2017/9372050
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/0271678X16662891$$o10.1177/0271678X16662891
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24573$$o10.1002/ana.24573
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20160380$$o10.1042/CS20160380
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrn3114$$o10.1038/nrn3114
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24607$$o10.1002/ana.24607
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.1592-13.2013$$o10.1523/JNEUROSCI.1592-13.2013
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24271$$o10.1002/ana.24271
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nm.2394$$o10.1038/nm.2394
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24006$$o10.1002/ana.24006
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jalz.2016.09.006$$o10.1016/j.jalz.2016.09.006
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.STR.0000058480.77236.B3$$o10.1161/01.STR.0000058480.77236.B3
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2007.07.015$$o10.1016/j.neurobiolaging.2007.07.015
000140199 999C5 $$2Crossref$$oRaja 2017$$y2017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.50.4.966$$o10.1212/WNL.50.4.966
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2014.12.032$$o10.1016/j.neuron.2014.12.032
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/0271678X16635657$$o10.1177/0271678X16635657
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/0271678X17706449$$o10.1177/0271678X17706449
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/jnnp.2009.172072$$o10.1136/jnnp.2009.172072
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0000000000004677$$o10.1212/WNL.0000000000004677
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0000000000003556$$o10.1212/WNL.0000000000003556
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neulet.2010.09.063$$o10.1016/j.neulet.2010.09.063
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/01.STR.27.11.2069$$o10.1161/01.STR.27.11.2069
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/01.wnl.0000319691.50117.54$$o10.1212/01.wnl.0000319691.50117.54
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.115.009589$$o10.1161/STROKEAHA.115.009589
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.110.611731$$o10.1161/STROKEAHA.110.611731
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.112.669994$$o10.1161/STROKEAHA.112.669994
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awg040$$o10.1093/brain/awg040
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0140-6736(99)00309-8$$o10.1016/S0140-6736(99)00309-8
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awh023$$o10.1093/brain/awh023
000140199 999C5 $$2Crossref$$oHupe 2017$$y2017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.devcel.2015.05.008$$o10.1016/j.devcel.2015.05.008
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.2946$$o10.1038/nn.2946
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature05193$$o10.1038/nature05193
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature13165$$o10.1038/nature13165
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2015.06.001$$o10.1016/j.neuron.2015.06.001
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1177/0271678X15610340$$o10.1177/0271678X15610340
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2010.09.043$$o10.1016/j.neuron.2010.09.043
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.4489$$o10.1038/nn.4489
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nm.4482$$o10.1038/nm.4482
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3389/fnene.2010.00005$$o10.3389/fnene.2010.00005
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2015.10.067$$o10.1016/j.cell.2015.10.067
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/bpa.12004$$o10.1111/bpa.12004
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3109/01913123.2011.620220$$o10.3109/01913123.2011.620220
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24512$$o10.1002/ana.24512
000140199 999C5 $$2Crossref$$oLiu 2017$$y2017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1440-1789.2011.01290.x$$o10.1111/j.1440-1789.2011.01290.x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/nan.12188$$o10.1111/nan.12188
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20160618$$o10.1042/CS20160618
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20170004$$o10.1042/CS20170004
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/jcbfm.2015.62$$o10.1038/jcbfm.2015.62
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s12987-015-0019-5$$o10.1186/s12987-015-0019-5
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrneurol.2015.119$$o10.1038/nrneurol.2015.119
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/bpa.12159$$o10.1111/bpa.12159
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0041636$$o10.1371/journal.pone.0041636
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.nbd.2016.05.015$$o10.1016/j.nbd.2016.05.015
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1172/JCI10498$$o10.1172/JCI10498
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2004.07.017$$o10.1016/j.neuron.2004.07.017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.nlm.2014.12.005$$o10.1016/j.nlm.2014.12.005
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1750-3639.2007.00094.x$$o10.1111/j.1750-3639.2007.00094.x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbr.2008.02.005$$o10.1016/j.bbr.2008.02.005
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3389/fnmol.2017.00144$$o10.3389/fnmol.2017.00144
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1197623$$o10.1126/science.1197623
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0b013e3182703fd2$$o10.1212/WNL.0b013e3182703fd2
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3390/brainsci4010150$$o10.3390/brainsci4010150
000140199 999C5 $$2Crossref$$oSpira 2013$$y2013
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-008-0457-0$$o10.1007/s00401-008-0457-0
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1750-3639.2008.00133.x$$o10.1111/j.1750-3639.2008.00133.x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbadis.2015.08.024$$o10.1016/j.bbadis.2015.08.024
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/BF03402043$$o10.1007/BF03402043
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.21300/18.1.2016.63$$o10.21300/18.1.2016.63
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.bbadis.2015.10.014$$o10.1016/j.bbadis.2015.10.014
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.114.006617$$o10.1161/STROKEAHA.114.006617
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.2112-16.2017$$o10.1523/JNEUROSCI.2112-16.2017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.3020-14.2014$$o10.1523/JNEUROSCI.3020-14.2014
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2016.11.002$$o10.1016/j.neurobiolaging.2016.11.002
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.3390-16.2017$$o10.1523/JNEUROSCI.3390-16.2017
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/s41598-017-00861-x$$o10.1038/s41598-017-00861-x
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroimage.2017.03.021$$o10.1016/j.neuroimage.2017.03.021
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1241224$$o10.1126/science.1241224
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/mrm.26779$$o10.1002/mrm.26779
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.108.528430$$o10.1161/STROKEAHA.108.528430
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1161/STROKEAHA.109.569855$$o10.1161/STROKEAHA.109.569855
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2015.09.010$$o10.1016/j.neurobiolaging.2015.09.010
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/s41598-018-19781-5$$o10.1038/s41598-018-19781-5
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3233/JAD-132528$$o10.3233/JAD-132528
000140199 999C5 $$2Crossref$$oBerezuk 2015$$y2015
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.aah4968$$o10.1126/science.aah4968
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1180962$$o10.1126/science.1180962
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s11936-017-0555-1$$o10.1007/s11936-017-0555-1
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/jmri.24047$$o10.1002/jmri.24047
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20170051$$o10.1042/CS20170051
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/ijs.12490$$o10.1111/ijs.12490
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s11604-017-0617-z$$o10.1007/s11604-017-0617-z
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.2967/jnumed.116.187211$$o10.2967/jnumed.116.187211
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20170146$$o10.1042/CS20170146
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20160452$$o10.1042/CS20160452
000140199 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1042/CS20160724$$o10.1042/CS20160724